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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.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.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 (β = .138, p = .042), and this result remained after adjusting for additional covariates (β = .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 (β = .307, p = .006), and this remained after accounting for initial symptoms and many covariates (β = .237, p = .021).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.

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).

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 fMRI 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 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 these neural differences were specific to those high on AB, but not CU traits. Neither AB, CU traits, nor their interaction were 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.

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,meanage=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 tor=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.

Racialized disparities in aging-related health may partially be driven by epigenetic processes related to accelerated biological aging6,7,8. Adversity in childhood, such as racial marginalization and low socioeconomic status (SES) has been associated with a faster pace of biological aging measured in DNAm in 8-to-18-year-old children from the Texas Twin Project9. Moreover, saliva DNAm quantification of the pace of biological aging statistically accounted for racialized disparities in internalizing symptoms. It remains unknown whether these findings generalize across cohorts, contexts, and development. The aim of this study is to explore racialized inequities in longitudinally assessed saliva DNAm measures of biological aging with mental health across childhood and adolescence. Participants will include n=2,020 children from the Future of Families and Child Well-being Study (FFCWS) in the USA with DNAm data collected at 9 years and 15 years of age. We will examine associations between individual’s race/ethnicity, neighborhood contexts (i.e., family-level and neighborhood-level racial/ethnic identities, SES, police interactions), saliva DNAm quantification of biological aging (i.e., DunedinPACE, GrimAge, PhenoAge subsumed as “DNAm-aging”), and mental health (i.e., parent-reported internalizing and externalizing behaviors from age 3 to 15; adolescent-reported depression and anxiety at age 15). We will employ latent growth curve models and cross-lagged panel models to assess multivariate longitudinal dynamics of racialized disparities and aging-related mental health10. Data has been collected.

The prevalence 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 Fragile 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 were analyzed on 796 children 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 at age 9 (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 theAMDHD2gene, 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 age 9 and age 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.

Background Both parental and neighbourhood socio-economic status (SES) are linked to poorer health independently of personal SES measures, but the biological mechanisms are unclear. Our objective was to examine these influences via epigenetic age acceleration (EAA)—the discrepancy between chronological and epigenetic ages. Methods We examined three USA-based [Coronary Artery Risk Disease in Adults (CARDIA) study, Fragile Families and Child Wellbeing Study (FFCWS) and Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS)] and one Mexico-based (Project Viva) cohort. DNA methylation was measured using Illumina arrays, personal/parental SES by questionnaire and neighbourhood disadvantage from geocoded address. In CARDIA, we examined the most strongly associated personal, parental and neighbourhood SES measures with EAA (Hannum’s method) at study years 15 and 20 separately and combined using a generalized estimating equation (GEE) and compared with other EAA measures (Horvath’s EAA, PhenoAge and GrimAge calculators, and DunedinPoAm). Results EAA was associated with paternal education in CARDIA [GEEs: βsome college = −1.01 years (−1.91, −0.11) and β Conclusions These findings suggest that EAA captures epigenetic impacts of paternal education independently of personal SES later in life. Longitudinal studies should explore these associations at different life stages and link them to health outcomes. EAA could be a useful biomarker of SES-associated health and provide important insight into the pathogenesis and prevention of chronic disease.

Saliva is a widely used biological sample, especially in pediatric research, containing a heterogenous mixture of immune and epithelial cells. Associations of exposure or disease with saliva DNA methylation can be influenced by cell-type proportions. Here, we developed a saliva cell-type DNA methylation reference panel to estimate interindividual cell-type heterogeneity in whole saliva studies. Saliva was collected from 22 children (7–16 years) and sorted into immune and epithelial cells, using size exclusion filtration and magnetic bead sorting. DNA methylation was measured using the Illumina MethylationEPIC BeadChip. We assessed cell-type differences in DNA methylation profiles and tested for enriched biological pathways. Immune and epithelial cells differed at 181,577 (22.8%) DNA methylation sites (t-test p

Childhood adversity is thought to undermine youth socioemotional development via altered neural function within regions that support emotion processing. These effects are hypothesized to be developmentally specific, with adversity in early childhood sculpting subcortical structures (e.g., amygdala) and adversity during adolescence impacting later-developing structures (e.g., prefrontal cortex; PFC). However, little work has tested these theories directly in humans. Using prospectively collected longitudinal data from the Fragile Families and Child Wellbeing Study (FFCWS) (N = 4,144) and neuroimaging data from a subsample of families recruited in adolescence (N = 162), the current study investigated the trajectory of harsh parenting across childhood (i.e., ages 3 to 9) and how initial levels versus changes in harsh parenting across childhood were associated with corticolimbic activation and connectivity during socioemotional processing. Harsh parenting in early childhood (indexed by the intercept term from a linear growth curve model) was associated with less amygdala, but not PFC, reactivity to angry facial expressions. In contrast, change in harsh parenting across childhood (indexed by the slope term) was associated with less PFC, but not amygdala, activation to angry faces. Increases in, but not initial levels of, harsh parenting were also associated with stronger positive amygdala–PFC connectivity during angry face processing.

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used Genomic Structural Equation Modeling and prior genome-wide association studies (GWAS) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability.We identified 157 genome-wide significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Non-cognitive genetics were enriched in the same brain tissues and cell types as cognitive performance but showed different associations with gray-matter brain volumes. Non-cognitive genetics were further distinguished by associations with personality traits, less risky behavior,and increased risk for certain psychiatric disorders.For socioeconomic success and longevity, non-cognitive and cognitive-performance genetics demonstrated similar-magnitude associations. By conducting a GWAS of a phenotype that was not directly measured, we offer a first view of genetic architecture of non-cognitive skills influencing educational success.

Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1–15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1–15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.

Callous-unemotional (CU) traits have recently been added to the diagnostic criteria of Conduct Disorder in the Diagnostic and Statistical Manual of Mental Disorders–Fifth edition and of conduct–dissocial and oppositional defiant disorders in the International Classification of Disease–Eleventh edition as the limited prosocial emotions specifier. This change necessitates the assessment of these traits with validated measures in both research and clinical contexts. The current study sought to validate a semi-structured diagnostic interview method, the Michigan Limited Prosocial Emotion Addendum (M-LPE) to the Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version, of assessing CU traits based on a recently developed clinician rating system (Clinical Assessment of Prosocial Emotions, Version 1.1) in a sample of at-risk youth. Results supported the interrater reliability of the M-LPE with moderate agreement and high reliability between raters. The M-LPE demonstrated convergent and incremental validity with CU traits and various measures of antisocial behavior. The results provide preliminary evidence for the use of a semi-structured interview assessment of CU traits in research contexts and build the foundation for further validation.

Prominent theories suggest that disruptions in amygdala reactivity and connectivity when processing emotional cues are key to the etiology of youth antisocial behavior (AB) and that these associations may be dependent on co-occurring levels of callous-unemotional (CU) traits. We examined the associations among AB, CU traits, and amygdala reactivity and functional connectivity while viewing emotional faces (fearful, angry, sad, happy) in 165 adolescents (46% male; 73.3% African American) from a representative, predominantly low-income community sample. AB was associated with increased amygdala activation in response to all emotions and was associated with greater amygdala reactivity to emotion only at low levels of CU traits. AB and CU traits were also associated with distinct patterns of amygdala connectivity. These findings demonstrate that AB-related deficits in amygdala functioning may extend across all emotions and highlight the need for further research on amygdala connectivity during emotion processing in relation to AB and CU traits within community populations.

Gun violence is a major public health problem and costs the United States $280 billion annually (1). Although adolescents are disproportionately impacted (e.g. premature death), we know little about how close adolescents live to deadly gun violence incidents and whether such proximity impacts their socioemotional development (2, 3). Moreover, gun violence is likely to shape youth developmental outcomes through biological processes—including functional connectivity within regions of the brain that support emotion processing, salience detection, and physiological stress responses—though little work has examined this hypothesis. Lastly, it is unclear if strong neighborhood social ties can buffer youth from the neurobehavioral effects of gun violence. Within a nationwide birth cohort of 3,444 youth (56% Black, 24% Hispanic) born in large US cities, every additional deadly gun violence incident that occurred within 500 meters of home in the prior year was associated with an increase in behavioral problems by 9.6%, even after accounting for area-level crime and socioeconomic resources. Incidents that occurred closer to a child's home exerted larger effects, and stronger neighborhood social ties offset these associations. In a neuroimaging subsample (N = 164) of the larger cohort, living near more incidents of gun violence and reporting weaker neighborhood social ties were associated with weaker amygdala–prefrontal functional connectivity during socioemotional processing, a pattern previously linked to less effective emotion regulation. Results provide spatially sensitive evidence for gun violence effects on adolescent behavior, a potential mechanism through which risk is biologically embedded, and ways in which positive community factors offset ecological risk.

Accumulating literature has linked poverty to brain structure and function, particularly in affective neural regions; however, few studies have examined associations with structural connections or the importance of developmental timing of exposure. Moreover, prior neuroimaging studies have not used a proximal measure of poverty (i.e., material hardship, which assesses food, housing, and medical insecurity) to capture the lived experience of growing up in harsh economic conditions. The present investigation addressed these gaps collectively by examining the associations between material hardship (ages 1, 3, 5, 9, and 15 years) and white matter connectivity of frontolimbic structures (age 15 years) in a low-income sample. We applied probabilistic tractography to diffusion imaging data collected from 194 adolescents. Results showed that material hardship related to amygdala–prefrontal, but not hippocampus–prefrontal or hippocampus–amygdala, white matter connectivity. Specifically, hardship during middle childhood (ages 5 and 9 years) was associated with greater connectivity between the amygdala and dorsomedial pFC, whereas hardship during adolescence (age 15 years) was related to reduced amygdala–orbitofrontal (OFC) and greater amygdala–subgenual ACC connectivity. Growth curve analyses showed that greater increases of hardship across time were associated with both greater (amygdala–subgenual ACC) and reduced (amygdala–OFC) white matter connectivity. Furthermore, these effects remained above and beyond other types of adversity, and greater hardship and decreased amygdala–OFC connectivity were related to increased anxiety and depressive symptoms. Results demonstrate that the associations between material hardship and white matter connections differ across key prefrontal regions and developmental periods, providing support for potential windows of plasticity for structural circuits that support emotion processing.

Background: Prenatal maternal smoking has negative implications for child health. DNA methylation signatures can function as biomarkers of prenatal maternal smoking. However little work has assessed how DNA methylation signatures of prenatal maternal smoking vary across ages, ancestry groups, or tissues. In the Fragile Families and Child Wellbeing study, we tested whether prenatal maternal smoking was associated with salivary polymethylation scores for smoking in participants. We assessed the consistency of associations at ages 9 and 15, their portability across participants from African, European, and Hispanic genetic ancestries and the accuracy of exposure classification using area under the curve (AUC) from receiver operating curve analyses. Results: We created saliva polymethylation scores using coefficients from a meta-analysis of prenatal maternal smoke exposure and DNA methylation in newborn cord blood. In the full sample at age 9 (n=753), prenatal maternal smoke exposure was associated with a 0.52 (95%CI: 0.36, 0.67) standard deviation higher polymethylation score for prenatal smoke exposure The direction and magnitude of the association was consistent when stratified by genetic ancestries. In the full sample at age 15 (n=746), prenatal maternal smoke exposure was associated with a 0.46 (95%CI: 0.3, 0.62) standard deviation higher polymethylation score for prenatal smoke exposure, and the effect size was attenuated among the European and Hispanic genetic ancestry samples. The polymethylation score was reasonably accurate at classifying prenatal maternal smoke exposure (AUC age 9=0.77, P value

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.

Exposure in utero to particulate matter (PM2.5 and PM10) is associated with maladaptive health outcomes. Although exposure to prenatal PM2.5 and PM10 has cord blood DNA methylation signatures at birth, signature persistence into childhood and saliva cross-tissue applicability has not been tested. In the Fragile Families and Child Wellbeing Study, a United States 20-city birth cohort, average residential PM2.5 and PM10 during the three months prior to birth was estimated using air quality monitors with inverse distance weighting. Saliva DNA methylation at ages 9 (n = 749) and 15 (n = 793) was measured using the Illumina HumanMethylation 450 k BeadArray. Cumulative DNA methylation scores for particulate matter were estimated by weighting participant DNA methylation at each site by independent meta-analysis effect estimates and standardizing the sums. Using a mixed-effects regression analysis, we tested the associations between cumulative DNA methylation scores at ages 9 and 15 and PM exposure during pregnancy, adjusted for child sex, age, race/ethnicity, maternal income-to-needs ratio, nonmartial birth status, and saliva cell-type proportions. Our study sample was 50.5% male, 56.3% non-Hispanic Black, and 19.8% Hispanic, with a median income-to-needs ratio of 1.4. Mean exposure levels for PM2.5 were 27.9 μg/m3/day (standard deviation: 7.0; 23.7% of observations exceeded safety standards) and for PM10 were 15.0 μg/m3/day (standard deviation: 3.1). An interquartile range increase in PM2.5 exposure (10.73 μg/m3/day) was associated with a −0.0287 standard deviation lower cumulative DNA methylation score for PM2.5 (95% CI: −0.0732, 0.0158, p = 0.20) across all participants. An interquartile range increase in PM10 exposure (3.20 μg/m3/day) was associated with a −0.1472 standard deviation lower cumulative DNA methylation score for PM10 (95% CI: −0.3038, 0.0095, p = 0.06) across all participants. The PM10 findings were driven by the age 15 subset where an interquartile range increase in PM10 exposure was associated with a −0.024 standard deviation lower cumulative DNA methylation score for PM10 (95% CI: −0.043, −0.005, p = 0.012). Findings were robust to adjustment for PM exposure at ages 1 and 3. In utero PM10-associated DNA methylation differences were identified at age 15 in saliva. Benchmarking the timing and cell-type generalizability is critical for epigenetic exposure biomarker assessment.

Threat-related amygdala reactivity and the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis have been linked to negative psychiatric outcomes. The amygdala and HPA axis have bidirectional connections, suggesting that functional variation in one system may influence the other. However, research on the functional associations between these systems has demonstrated mixed findings, potentially due to small sample sizes and cortisol sampling and data analytic procedures that investigate only pre-post differences in cortisol rather than the specific phases of the cortisol stress response. Further, previous research has primarily utilized samples of adults of mostly European descent, limiting generalizability to those of other ethnoracial identities and ages. Therefore, studies addressing these limitations are needed in order to investigate the functional relations between amygdala reactivity to threat and HPA axis stress responsivity. Using a sample of 159 adolescents from a diverse cohort (75% African American, ages 15-17 years), the present study evaluated associations between amygdala reactivity during socioemotional processing using fMRI and HPA axis reactivity to a socially-evaluative cold pressor task. Greater amygdala activation to fearful and neutral faces was associated with greater cortisol peak values and steeper activation slope. As cortisol peak values and cortisol activation slope capture the intensity of the cortisol stress response, these data suggest that greater activation of the amygdala in response to social distress and ambiguity among adolescents may be related to hyper-reactivity of the HPA axis.

The ventral striatum (VS) is implicated in reward processing and motivation. Human and non-human primate studies demonstrate that the VS and prefrontal cortex (PFC), which comprise the frontostriatal circuit, interact to influence motivated behavior. However, there is a lack of research that precisely maps and quantifies VS-PFC white matter tracts. Moreover, no studies have linked frontostriatal white matter to VS activation. Using a multimodal neuroimaging approach with diffusion MRI (dMRI) and functional MRI (fMRI), the present study had two objectives: 1) to chart white matter tracts between the VS and specific PFC structures and 2) assess the association between the degree of VS-PFC white matter tract connectivity and VS activation in 187 adolescents. White matter connectivity was assessed with probabilistic tractography and functional activation was examined with two fMRI tasks (one task with social reward and another task using monetary reward). We found widespread but variable white matter connectivity between the VS and areas of the PFC, with the anterior insula and subgenual cingulate cortex demonstrating the greatest degree of connectivity with the VS. VS-PFC structural connectivity was related to functional activation in the VS though activation depended on the specific PFC region and reward task.

Reliable, brief, and cost-effective methods to assess parenting are critical for advancing etiological research and translational efforts within parenting science. In the current study, we adapted the System for Coding Interactions and Family Functioning (SCIFF) for use among a sample of mostly racial minority adolescents aged 15 years old, growing up in a low-income urban setting. A multiethnic team coded videotapes of a family interaction task designed to elicit conflict. First, we assessed the reliability of SCIFF codes (N = 187; 54% female; 77% African American). Second, we tested whether SCIFF codes assessing harsh parenting, positive parenting, dyadic conflict, and dyadic closeness converged with parent-child reports of the same constructs. Third we explored links between observed harsh and positive parenting in early childhood (ages 3 and 5) and SCIFF codes at age 15. Our training and SCIFF coding protocols produced high interrater reliability. In support of convergent validity, we found specificity in the associations between negative aspects of parenting across methods: the SCIFF harsh parenting and dyadic conflict codes uniquely converged with concurrent parent-child reports of the same constructs. There was a longitudinal cross-construct association between more observed harshness in early childhood and lower dyadic closeness at age 15. Finally, the convergence of the SCIFF codes with other parenting measures was similar by gender and for families living below or above 200% of the poverty line. A modified version of the SCIFF can be used with reliability in low-income urban samples with variation in gender and race. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Recent theory suggests that developmental idealism (DI) is an important source of variation and change in family behavior, yet this suggestion is largely untested at the individual level. This study examines the influence of DI beliefs and values on individuals’ entrance into marriage. We hypothesize that when individuals and their parents endorse DI, they enter into marriage later or more slowly. We also hypothesize that two pathways connecting DI to marriage are the instillation of older timing attitudes and expectations of marrying at older ages. We test these hypotheses using panel data collected in Nepal from 2008 to 2014. When young people and their parents endorsed DI, the young people valued older ages at marriage and expected to marry later. Young people’s own DI endorsement also delayed their entrance into marriage, but parents’ DI did not.

Despite prior extensive investigations of the interactions between the amygdala and prefrontal cortex, few studies have simultaneously considered activation and structural connectivity in this circuit, particularly as it pertains to adolescent socioemotional development. The current multi-modal study delineated the correspondence between uncinate fasciculus (UF) connectivity and amygdala habituation in a large adolescent sample that was drawn from a population-based sample. We then examined the influence of demographic variables (age, gender, and pubertal status) on the relation between UF connectivity and amygdala habituation. 106 participants (15-17 years) completed DTI and an fMRI emotional face processing task. Left UF fractional anisotropy was associated with left amygdala habituation to fearful faces, suggesting that increased structural connectivity of the UF may facilitate amygdala regulation. Pubertal status moderated this structure-function relation, such that the association was stronger in those who were less mature. Therefore, UF connectivity may be particularly important for emotion regulation during early puberty. This study is the first to link structural and functional limbic circuitry in a large adolescent sample with substantial representation of ethnic minority participants, providing a more comprehensive understanding of socioemotional development in an understudied population.

AO_SCPLOWBSTRACTC_SCPLOWThe Fragile Families Child Wellbeing Study (FFCWS) is a longitudinal cohort of ethnically diverse and primarily low socioeconomic status children and their families in the U.S. Here, we analyze DNA methylation data collected from 748 FFCWS participants in two waves of this study, corresponding to participant ages 9 and 15. Our primary goal is to leverage the DNA methylation data from these two time points to study methylation associated with two key traits in adolescent health that are over-represented in these data: Early puberty and teen depression. We first identify differentially methylated regions (DMRs) for depression and early puberty. We then identify DMRs for the interaction effects between these two conditions and age by including interaction terms in our regression models to understand how age-related changes in methylation are influenced by depression or early puberty. Next, we identify methylation quantitative trait loci (meQTLs) using genotype data from the participants. We also identify meQTLs with epistatic effects with depression and early puberty. We find enrichment of our interaction meQTLs with functional categories of the genome that contribute to the heritability of co-morbid complex diseases. We replicate our meQTLs in data from the GoDMC study. This work leverages the important focus of the FFCWS data on disadvantaged children to shed light on the methylation states associated with teen depression and early puberty, and on how genetic regulation of methylation is affected in adolescents with these two conditions.

ObjectiveAlzheimer disease (AD) is a common and costly neurodegenerative disorder. A large proportion of AD risk is heritable, and many genetic risk factors have been identified. The objective of this study was to test the hypothesis that cumulative genetic risk of known AD markers contributed to odds of dementia in a population-based sample.MethodsIn the US population-based Health and Retirement Study (waves 1995–2014), we evaluated the role of cumulative genetic risk of AD, with and without the APOE ε4 alleles, on dementia status (dementia, cognitive impairment without dementia, borderline cognitive impairment without dementia, and cognitively normal). We used logistic regression, accounting for demographic covariates and genetic principal components, and analyses were stratified by European and African genetic ancestry.ResultsIn the European ancestry sample (n = 8,399), both AD polygenic score excluding the APOE genetic region (odds ratio [OR] = 1.10; 95% confidence interval [CI]: 1.00–1.20) and the presence of any APOE ε4 alleles (OR = 2.42; 95% CI: 1.99–2.95) were associated with the odds of dementia relative to normal cognition in a mutually adjusted model. In the African ancestry sample (n = 1,605), the presence of any APOE ε4 alleles was associated with 1.77 (95% CI: 1.20–2.61) times higher odds of dementia, whereas the AD polygenic score excluding the APOE genetic region was not significantly associated with the odds of dementia relative to normal cognition 1.06 (95% CI: 0.97–1.30).ConclusionsCumulative genetic risk of AD and APOE ε4 are both independent predictors of dementia in European ancestry. This study provides important insight into the polygenic nature of dementia and demonstrates the utility of polygenic scores in dementia research.

Background Telomere length (TL) in peripheral blood mononuclear cells (PBMC) from fresh venous blood is increasingly used to estimate molecular impacts of accumulated social adversity on population health. Sometimes, TL extracted from saliva or dried blood spots (DBS) are substituted as less invasive and more scalable specimen collection methods; yet, are they interchangeable with fresh blood? Studies find TL is correlated across tissues, but have not addressed the critical question for social epidemiological applications: Do different specimen types show the same association between TL and social constructs? Methods We integrate expertise in social epidemiology, molecular biology, and the statistical impact of measurement error on parameter estimates. Recruiting a diverse sample of 132 Metro-Detroit women, we measure TL for each woman from fresh blood PBMC, DBS, and saliva. Using regression methods, we estimate associations between social characteristics and TL, comparing estimates across specimen types for each woman. Results Associations between TL and social characteristics vary by specimen type collected from the same woman, sometimes qualitatively altering estimates of the magnitude or direction of a theorized relationship. Being Black is associated with shorter TL in PBMC, but longer TL in saliva or DBS. Education is positively associated with TL in fresh blood, but negatively associated with TL using DBS. Conclusion Findings raise concerns about the use of TL measures derived from different tissues in social epidemiological research. Investigators need to consider the possibility that associations between social variables and TL may be systematically related to specimen type, rather than be valid indicators of socially-patterned biopsychosocial processes.

Objective Ethnic/racial minority children in the United States are more likely to experience father loss to incarceration than White children, and limited research has examined the health implications of these ethnic/racial disparities. Telomere length is a biomarker of chronic stress that is predictive of adverse health outcomes. This study examined whether paternal incarceration predicted telomere length shortening among offspring from childhood to adolescence, whether maternal depression mediated the link, and whether ethnicity/race moderated results. Method Research participants included 2,395 families in the Fragile Families and Child Wellbeing study, a national and longitudinal cohort study of primarily low-income families from 20 large cities in the United States. Key constructs were measured when children were on average ages 9 (2007–2010) and 15 (2014–2017). Results Children who experienced paternal incarceration exhibited shorter telomere lengths between ages 9 and 15, and changes in maternal depression mediated this finding. Specifically, mothers who experienced a partner’s incarceration were more likely to have depression between children’s ages 9 and 15. In turn, increases in maternal depression between children’s ages 9 and 15 predicted more accelerated telomere length shortening among children during this period. Paternal incarceration was more prevalent and frequent for ethnic/racial minority youth than for White youth. Conclusion Paternal incarceration is associated with a biomarker of chronic stress among children in low-income families. Rates of paternal incarceration were more prevalent and frequent among Black American and multiethnic/multiracial families than among White Americans. As a result, the mass incarceration crisis of the criminal justice system is likely shaping intergenerational ethnic/racial health disparities.

Manuscript in press at Development & Psychopathology (Submitted 8/17/2020, Accepted 11/08/2020). Childhood adversity is thought to undermine youth socioemotional development via altered neural function within regions that support emotion processing. These effects are hypothesized to be developmentally specific, with adversity in early childhood sculpting subcortical structures (e.g., amygdala) and adversity during adolescence impacting later-developing structures (e.g., prefrontal cortex; PFC). However, little work has tested these theories directly in humans. Using prospectively-collected longitudinal data from the Fragile Families and Child Wellbeing Study (N = 4,144) and neuroimaging data from a subsample of families recruited in adolescence (N = 162), the current study investigated the trajectory of harsh parenting across childhood (i.e., ages 3 to 9) and how initial levels versus changes in harsh parenting across childhood were associated with corticolimbic activation and connectivity during socioemotional processing. Harsh parenting in early childhood (indexed by the intercept term from a linear growth curve model) was associated with less amygdala, but not PFC, reactivity to angry facial expressions. In contrast, change in harsh parenting across childhood (indexed by the slope term) was associated with less PFC, but not amygdala, activation to angry faces. Increases in, but not initial levels of, harsh parenting were also associated with stronger positive amygdala-PFC connectivity during angry face processing

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Saliva is a widely used biological sample, especially in pediatric research, containing a heterogenous mixture of immune and epithelial cells. Associations of exposure or disease with saliva DNA methylation can be influenced by cell-type proportions. Here, we developed a saliva cell-type DNA methylation reference panel to estimate interindividual cell-type heterogeneity in whole saliva studies. Saliva was collected from 22 children (7-16 years) and sorted into immune and epithelial cells, using size exclusion filtration and magnetic bead sorting. DNA methylation was measured using the Illumina MethylationEPIC BeadChip. We assessed cell-type differences in DNA methylation profiles and tested for enriched biological pathways. Immune and epithelial cells differed at 164,793 (20.7%) DNA methylation sites (t-test p < 10-8). Immune cell hypomethylated sites mapped to genes enriched for immune pathways (p < 3.2 × 10-5). Epithelial cell hypomethylated sites were enriched for cornification (p = 5.2 × 10-4), a key process for hard palette formation. Saliva immune and epithelial cells have distinct DNA methylation profiles which can drive whole saliva DNA methylation measures. A primary saliva DNA methylation reference panel, easily implemented with an R package, will allow estimates of cell proportions from whole saliva samples and improve epigenetic epidemiology studies by accounting for measurement heterogeneity by cell-type proportions.

Key Points Question Are violence exposure and social deprivation associated with person-specific patterns (heterogeneity) of adolescent resting-state functional connectivity? Findings In this cohort study of 175 adolescents, childhood violence exposure, but not social deprivation, was associated with reduced adolescent resting-state density of the salience and default mode networks. A data-driven algorithm, blinded to childhood adversity, identified youth with heightened violence exposure based on resting-state connectivity patterns. Meaning Childhood violence exposure appears to be associated with adolescent functional connectivity heterogeneity, which may reflect person-specific neural plasticity and should be considered in neuroscience-based interventions., Importance Adverse childhood experiences are a public health issue with negative sequelae that persist throughout life. Current theories suggest that adverse childhood experiences reflect underlying dimensions (eg, violence exposure and social deprivation) with distinct neural mechanisms; however, research findings have been inconsistent, likely owing to variability in how the environment interacts with the brain. Objective To examine whether dimensional exposure to childhood adversity is associated with person-specific patterns in adolescent resting-state functional connectivity (rsFC), defined as synchronized activity across brain regions when not engaged in a task. Design, Setting, and Participants A sparse network approach in a large sample with substantial representation of understudied, underserved African American youth was used to conduct an observational, population-based longitudinal cohort study. A total of 183 adolescents aged 15 to 17 years from Detroit, Michigan; Toledo, Ohio; and Chicago, Illinois, who participated in the Fragile Families and Child Wellbeing Study were eligible for inclusion. Environmental data from birth to adolescence were collected via telephone and in-person interviews, and neuroimaging data collected at a university lab. The study was conducted from February 1, 1998, to April 26, 2017, and data analysis was performed from January 3, 2019, to May 22, 2020. Exposures Composite variables representing violence exposure and social deprivation created from primary caregiver reports on children at ages 3, 5, and 9 years. Main Outcomes and Measures Resting-state functional connectivity person-specific network metrics (data-driven subgroup membership, density, and node degree) focused on connectivity among a priori regions of interest in 2 resting-state networks (salience network and default mode) assessed with functional magnetic resonance imaging. Results Of the 183 eligible adolescents, 175 individuals (98 girls [56%]) were included in the analysis; mean (SD) age was 15.88 (0.53) years and 127 participants (73%) were African American. Adolescents with high violence exposure were 3.06 times more likely (95% CI, 1.17-8.92) to be in a subgroup characterized by high heterogeneity (few shared connections) and low network density (sparsity). Childhood violence exposure, but not social deprivation, was associated with reduced rsFC density (β = −0.25; 95% CI, −0.41 to −0.05; P = .005), with fewer salience network connections (β = −0.26; 95% CI, −0.43 to −0.08; P = .005) and salience network-default mode connections (β = −0.20; 95% CI, −0.38 to −0.03; P = .02). Violence exposure was associated with node degree of right anterior insula (β = −0.29; 95% CI, −0.47 to −0.12; P = .001) and left inferior parietal lobule (β = −0.26; 95% CI, −0.44 to −0.09; P = .003). Conclusions and Relevance The findings of this study suggest that childhood violence exposure is associated with adolescent neural network sparsity. A community-detection algorithm, blinded to child adversity, grouped youth exposed to heightened violence based only on patterns of rsFC. The findings may have implications for understanding how dimensions of adverse childhood experiences impact individualized neural development., This cohort study examines functional connectivity in adolescents who were exposed to violence during childhood.